Several experimental approaches have indicated that the vestibular system influences activity of respiratory "pump" muscles as well as particular upper airway muscles. During the tenure of the currently-funded grant, removal of vestibular inputs was shown to alter the resting activity of both the diaphragm and abdominal musculature, and to diminish changes in abdominal muscle activity that ordinarily occur during postural alterations. Furthermore, experiments employing the transneuronal transport of pseudorabies virus demonstrated that in addition to cells in the respiratory groups, neurons in the medial medullary reticular formation provide inputs to a variety of respiratory motoneurons. We propose to extend this work by testing the following general hypothesis: medial medullary reticular formation neurons that receive vestibular inputs globally modulate the excitability of both particular upper airway respiratory muscles and respiratory pump muscles during postural changes. Furthermore, we will explore the physiological significance of the observation that stimulation of regions of the cerebellum that receive vestibular inputs alters respiratory activity. Four specific aims are proposed. The first specific aim will determine whether removal of vestibular inputs alters spontaneous activity and tilt-related responses of upper airway respiratory muscles in awake animals. The second specific aim will ascertain whether common inhibitory medial reticular formation neurons provide inputs to motoneurons innervating upper airway and respiratory pump muscles. The third specific aim will establish whether medial medullary reticular formation neurons have appropriate responses to vestibular stimulation to mediate vestibulorespiratory reflexes. The fourth specific aim will determine whether ablation of cerebellar regions known to alter respiratory activity when stimulated will affect spontaneous activity and responses to tilt of respiratory pump muscles in awake animals. In combination, these experiments will extend knowledge concerning the physiological significance of vestibular influences on respiratory regulation, and will also elucidate the role of the medial medullary reticular formation in producing these responses. These findings may have relevance to humans, as a deficiency in vestibulo-respiratory responses could result in an insufficiency of respiratory adjustments during changes in posture, and could contribute to snoring and obstructive sleep apnea.